CL2017002284A1 - Use of substituted 2,3-dihydroimidazo [1,2-c] quinazolines. - Google Patents
Use of substituted 2,3-dihydroimidazo [1,2-c] quinazolines.Info
- Publication number
- CL2017002284A1 CL2017002284A1 CL2017002284A CL2017002284A CL2017002284A1 CL 2017002284 A1 CL2017002284 A1 CL 2017002284A1 CL 2017002284 A CL2017002284 A CL 2017002284A CL 2017002284 A CL2017002284 A CL 2017002284A CL 2017002284 A1 CL2017002284 A1 CL 2017002284A1
- Authority
- CL
- Chile
- Prior art keywords
- compound
- pharmaceutical composition
- line
- type
- pten
- Prior art date
Links
- NTTQCLSBWRKUIJ-UHFFFAOYSA-N 2,3-dihydroimidazo[1,2-c]quinazoline Chemical class C1=CC=C2C3=NCCN3C=NC2=C1 NTTQCLSBWRKUIJ-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 abstract 6
- 239000013543 active substance Substances 0.000 abstract 5
- 239000008194 pharmaceutical composition Substances 0.000 abstract 4
- 102000014160 PTEN Phosphohydrolase Human genes 0.000 abstract 3
- 108010011536 PTEN Phosphohydrolase Proteins 0.000 abstract 3
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 abstract 2
- 206010014733 Endometrial cancer Diseases 0.000 abstract 2
- 206010014759 Endometrial neoplasm Diseases 0.000 abstract 2
- 201000009273 Endometriosis Diseases 0.000 abstract 2
- 102100028138 F-box/WD repeat-containing protein 7 Human genes 0.000 abstract 2
- 101710105178 F-box/WD repeat-containing protein 7 Proteins 0.000 abstract 2
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 abstract 2
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 abstract 2
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 abstract 2
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 abstract 2
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 abstract 2
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 abstract 2
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 abstract 2
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 abstract 2
- 101001120056 Homo sapiens Phosphatidylinositol 3-kinase regulatory subunit alpha Proteins 0.000 abstract 2
- 101001120097 Homo sapiens Phosphatidylinositol 3-kinase regulatory subunit beta Proteins 0.000 abstract 2
- 101001098116 Homo sapiens Phosphatidylinositol 3-kinase regulatory subunit gamma Proteins 0.000 abstract 2
- 101000605639 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Proteins 0.000 abstract 2
- 101000595741 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Proteins 0.000 abstract 2
- 101000595746 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Proteins 0.000 abstract 2
- 101000595751 Homo sapiens Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Proteins 0.000 abstract 2
- 101000692672 Homo sapiens Phosphoinositide 3-kinase regulatory subunit 4 Proteins 0.000 abstract 2
- 101000692678 Homo sapiens Phosphoinositide 3-kinase regulatory subunit 5 Proteins 0.000 abstract 2
- 102100026169 Phosphatidylinositol 3-kinase regulatory subunit alpha Human genes 0.000 abstract 2
- 102100026177 Phosphatidylinositol 3-kinase regulatory subunit beta Human genes 0.000 abstract 2
- 102100037553 Phosphatidylinositol 3-kinase regulatory subunit gamma Human genes 0.000 abstract 2
- 102100038332 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform Human genes 0.000 abstract 2
- 102100036061 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform Human genes 0.000 abstract 2
- 102100036056 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform Human genes 0.000 abstract 2
- 102100036052 Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform Human genes 0.000 abstract 2
- 102100026481 Phosphoinositide 3-kinase regulatory subunit 4 Human genes 0.000 abstract 2
- 102100026478 Phosphoinositide 3-kinase regulatory subunit 5 Human genes 0.000 abstract 2
- 102000001742 Tumor Suppressor Proteins Human genes 0.000 abstract 2
- 108010040002 Tumor Suppressor Proteins Proteins 0.000 abstract 2
- 238000000034 method Methods 0.000 abstract 2
- 230000000306 recurrent effect Effects 0.000 abstract 2
- 230000035945 sensitivity Effects 0.000 abstract 2
- -1 2,3-dihydroimidazo [1,2-c] quinazoline compound Chemical class 0.000 abstract 1
- 206010028980 Neoplasm Diseases 0.000 abstract 1
- 230000004075 alteration Effects 0.000 abstract 1
- 239000000090 biomarker Substances 0.000 abstract 1
- 201000011510 cancer Diseases 0.000 abstract 1
- 239000003814 drug Substances 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
- A61K31/5375—1,4-Oxazines, e.g. morpholine
- A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q1/00—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
- C12Q1/68—Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
- C12Q1/6876—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
- C12Q1/6883—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
- C12Q1/6886—Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/106—Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism
-
- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12Q—MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
- C12Q2600/00—Oligonucleotides characterized by their use
- C12Q2600/158—Expression markers
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Genetics & Genomics (AREA)
- Zoology (AREA)
- Epidemiology (AREA)
- Wood Science & Technology (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Pathology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Hospice & Palliative Care (AREA)
- Physics & Mathematics (AREA)
- General Engineering & Computer Science (AREA)
- Biotechnology (AREA)
- Microbiology (AREA)
- Molecular Biology (AREA)
- Oncology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Endocrinology (AREA)
- Reproductive Health (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Saccharide Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Hydrogenated Pyridines (AREA)
Abstract
<p>La presente invención se refiere a: – uso de un compuesto de 2,3–dihidroimidazo[1,2–c]quinazolina o de una composición farmacéutica que lo contiene, como un único agente activo o de una combinación de a) dicho compuesto o una composición farmacéutica que contiene dicho compuesto y b) uno o varios otros agentes activos, para la preparación de un medicamento para el tratamiento o la prevención de cáncer de endometrio (de ahora en más en la presente, abreviado como “EC”), en particular EC de primera línea, de segunda línea, recurrente, refractario, de tipo I o de tipo II o endometriosis; – combinaciones de a) dicho compuesto y b) uno o varios otros agentes activos; – una composición farmacéutica que comprende dicho compuesto como un único agente activo para el tratamiento de cáncer de endometrio (de ahora en más en la presente, abreviado como “EC”), en particular EC de primera línea, de segunda línea, recurrente, refractario, de tipo I o de tipo II o endometriosis; – una composición farmacéutica que comprende una combinación de a) dicho compuesto y b) uno o varios otros agentes activos; – uso de biomarcadores que es la pérdida de supresor tumoral PTEN o FBXW7, para predecir la sensibilidad y/o la resistencia de un paciente con cáncer a dicho compuesto y suministro de una dosis racional para incrementar la sensibilidad y/o para superar la resistancia; – un método de determinación de la pérdida de supresor tumoral PTEN o FBXW7; y un método de determinación de perturbaciones en PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R4, PIK3R5, FGFR1, FGFR2, FGFR3 y/o FGFR4; pérdida y alteración de PTEN de PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R4, PIK3R5, FGFR1, FGFR2, FGFR3 y/o FGFR4.</p><p> The present invention relates to: - use of a 2,3-dihydroimidazo [1,2-c] quinazoline compound or a pharmaceutical composition containing it, as a single active agent or a combination of a) said compound or a pharmaceutical composition containing said compound and b) one or more other active agents, for the preparation of a medicament for the treatment or prevention of endometrial cancer (hereinafter, abbreviated as "EC") , in particular first-line, second-line, recurrent, refractory, type I or type II or endometriosis EC; - combinations of a) said compound and b) one or more other active agents; - a pharmaceutical composition comprising said compound as a single active agent for the treatment of endometrial cancer (hereinafter, abbreviated as "EC"), in particular first-line, second-line, recurrent, refractory EC , type I or type II or endometriosis; - a pharmaceutical composition comprising a combination of a) said compound and b) one or more other active agents; - use of biomarkers that is the loss of PTEN or FBXW7 tumor suppressor, to predict the sensitivity and / or resistance of a cancer patient to said compound and supply of a rational dose to increase sensitivity and / or to overcome resistance; - a method of determining the loss of PTEN or FBXW7 tumor suppressor; and a disturbance determination method in PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R4, PIK3R5, FGFR1, FGFR2, FGFR3 and / or FGFR4; PTEN loss and alteration of PIK3CA, PIK3CB, PIK3CD, PIK3CG, PIK3R1, PIK3R2, PIK3R3, PIK3R4, PIK3R5, FGFR1, FGFR2, FGFR3 and / or FGFR4. </p>
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562130547P | 2015-03-09 | 2015-03-09 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CL2017002284A1 true CL2017002284A1 (en) | 2018-05-18 |
Family
ID=55484986
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CL2017002284A CL2017002284A1 (en) | 2015-03-09 | 2017-09-08 | Use of substituted 2,3-dihydroimidazo [1,2-c] quinazolines. |
Country Status (18)
| Country | Link |
|---|---|
| US (1) | US20180042929A1 (en) |
| EP (1) | EP3268005A1 (en) |
| JP (1) | JP2018512403A (en) |
| KR (1) | KR20180013850A (en) |
| CN (1) | CN107683138A (en) |
| AU (1) | AU2016231260A1 (en) |
| BR (1) | BR112017019190A2 (en) |
| CA (1) | CA2978807A1 (en) |
| CL (1) | CL2017002284A1 (en) |
| EA (1) | EA201791975A1 (en) |
| HK (1) | HK1250645A1 (en) |
| IL (1) | IL254168A0 (en) |
| MA (1) | MA43840A (en) |
| MX (1) | MX2017011607A (en) |
| PH (1) | PH12017501644A1 (en) |
| SG (1) | SG11201707239WA (en) |
| TN (1) | TN2017000385A1 (en) |
| WO (1) | WO2016142313A1 (en) |
Families Citing this family (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2168583A1 (en) | 2008-09-24 | 2010-03-31 | Bayer Schering Pharma Aktiengesellschaft | Use of substituted 2,3-dihydroimidazo[1,2-c]quinazolines for the treatment of myeloma |
| EP2508525A1 (en) * | 2011-04-05 | 2012-10-10 | Bayer Pharma Aktiengesellschaft | Substituted 2,3-dihydroimidazo[1,2-c]quinazoline salts |
| JP6368353B2 (en) | 2013-04-08 | 2018-08-01 | バイエル ファーマ アクチエンゲゼルシャフト | Use of substituted 2,3-dihydroimidazo [1,2-c] quinazolines for the treatment of lymphoma |
| EP3018127A1 (en) | 2014-11-07 | 2016-05-11 | Bayer Pharma Aktiengesellschaft | Synthesis of copanlisib and its dihydrochloride salt |
| WO2016142312A1 (en) | 2015-03-09 | 2016-09-15 | Bayer Pharma Aktiengesellschaft | Substituted 2,3-dihydroimidazo[1,2-c]quinazoline-containing combinations |
| WO2017153220A1 (en) | 2016-03-08 | 2017-09-14 | Bayer Pharma Aktiengesellschaft | 2—amino—n— [7—methoxy—2, 3-dihydroimidazo-[1, 2-c] quinazolin-5-yl] pyrimidine—5—carboxamides |
| TWI794171B (en) | 2016-05-11 | 2023-03-01 | 美商滬亞生物國際有限公司 | Combination therapies of hdac inhibitors and pd-l1 inhibitors |
| TWI808055B (en) | 2016-05-11 | 2023-07-11 | 美商滬亞生物國際有限公司 | Combination therapies of hdac inhibitors and pd-1 inhibitors |
| US11185549B2 (en) | 2017-06-28 | 2021-11-30 | Bayer Consumer Care Ag | Combination of a PI3K-inhibitor with an androgen receptor antagonist |
| CN111500587A (en) * | 2020-04-15 | 2020-08-07 | 湖南省科域生物医药科技有限公司 | Application of PGR (platelet-rich protein) as product for treating endometriosis and PGR detection kit |
| US20230176059A1 (en) * | 2020-05-01 | 2023-06-08 | Mayo Foundation For Medical Education And Research | Methods and materials for treating endometrial cancer |
| WO2022140467A1 (en) * | 2020-12-21 | 2022-06-30 | Samson Pharma, Llc | Topical compositions and methods of treating skin diseases and conditions with such compositions |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20080306057A1 (en) * | 2005-10-11 | 2008-12-11 | Laboratories Serono Sa | P13K Inhibitors for the Treatment of Endometriosis |
| AR064106A1 (en) * | 2006-12-05 | 2009-03-11 | Bayer Schering Pharma Ag | DERIVATIVES OF 2,3-DIHYDROIMIDAZO [1,2-C] SUBSTITUTED QUINAZOLINE USEFUL FOR THE TREATMENT OF HYPER-PROLIFERATIVE DISEASES ASSOCIATED WITH ANGIOGENESIS |
| MA34158B1 (en) * | 2010-04-16 | 2013-04-03 | Bayer Ip Gmbh | COMBINATIONS CONTAINING SUBSTITUTED 2,3-DIHYDROIMIDAZO {1,2-C] QUINAZOLINE |
| EP2508525A1 (en) * | 2011-04-05 | 2012-10-10 | Bayer Pharma Aktiengesellschaft | Substituted 2,3-dihydroimidazo[1,2-c]quinazoline salts |
| EP3003377A1 (en) * | 2013-05-31 | 2016-04-13 | Novartis AG | Combination therapy containing a pi3k-alpha inhibitor and fgfr kinase inhibitor for treating cancer |
-
2016
- 2016-03-07 AU AU2016231260A patent/AU2016231260A1/en not_active Abandoned
- 2016-03-07 SG SG11201707239WA patent/SG11201707239WA/en unknown
- 2016-03-07 MA MA043840A patent/MA43840A/en unknown
- 2016-03-07 US US15/557,036 patent/US20180042929A1/en not_active Abandoned
- 2016-03-07 CA CA2978807A patent/CA2978807A1/en not_active Abandoned
- 2016-03-07 KR KR1020177027607A patent/KR20180013850A/en not_active Withdrawn
- 2016-03-07 EP EP16708402.9A patent/EP3268005A1/en not_active Withdrawn
- 2016-03-07 EA EA201791975A patent/EA201791975A1/en unknown
- 2016-03-07 BR BR112017019190A patent/BR112017019190A2/en not_active Application Discontinuation
- 2016-03-07 JP JP2017548211A patent/JP2018512403A/en not_active Withdrawn
- 2016-03-07 CN CN201680022080.8A patent/CN107683138A/en active Pending
- 2016-03-07 TN TNP/2017/000385A patent/TN2017000385A1/en unknown
- 2016-03-07 HK HK18110118.6A patent/HK1250645A1/en unknown
- 2016-03-07 WO PCT/EP2016/054728 patent/WO2016142313A1/en not_active Ceased
- 2016-03-07 MX MX2017011607A patent/MX2017011607A/en unknown
-
2017
- 2017-08-27 IL IL254168A patent/IL254168A0/en unknown
- 2017-09-08 PH PH12017501644A patent/PH12017501644A1/en unknown
- 2017-09-08 CL CL2017002284A patent/CL2017002284A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112017019190A2 (en) | 2018-04-24 |
| EA201791975A1 (en) | 2018-03-30 |
| WO2016142313A1 (en) | 2016-09-15 |
| KR20180013850A (en) | 2018-02-07 |
| EP3268005A1 (en) | 2018-01-17 |
| JP2018512403A (en) | 2018-05-17 |
| US20180042929A1 (en) | 2018-02-15 |
| IL254168A0 (en) | 2017-10-31 |
| CA2978807A1 (en) | 2016-09-15 |
| SG11201707239WA (en) | 2017-10-30 |
| HK1250645A1 (en) | 2019-01-11 |
| MA43840A (en) | 2018-11-21 |
| PH12017501644A1 (en) | 2018-03-12 |
| MX2017011607A (en) | 2018-04-10 |
| CN107683138A (en) | 2018-02-09 |
| TN2017000385A1 (en) | 2019-01-16 |
| AU2016231260A1 (en) | 2017-09-21 |
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